PROJECT SUMMARY Influenza epidemic control is an important public health priority, and the application of isolation, vaccination, and drug treatment measures to control influenza is based on an incomplete understanding of influenza virus epidemiology. Several limited studies suggest that influenza vaccination of children significantly reduces the disease burden in adult populations, but the extent of this effect is not known. The central hypothesis of this research is that the extent and severity of epidemic influenza largely depends on virus transmission in children. Three specific aims are proposed. In Specific Aim 1 we will track the appearance of influenza A and B in adults and children over five consecutive seasons to define patterns of virus spread within human populations, and test the hypothesis that the virus moves from children to adults. In Specific Aim 2 we will measure the impact of childhood vaccination, including the recently expanded nasal influenza vaccine indication for healthy persons 2-49 years of age, on the disease burden in both adults and children. We will concurrently determine influenza vaccination rates and rates of influenza disease in persons of all ages to measure the extent of influenza disease protection conferred to adults by childhood vaccination programs. In Specific Aim 3 we will measure influenza virus vaccine effectiveness for prevention of hospitalization and emergency department visits for persons of all ages. Dr. Poehling performed an important population-based epidemiologic study of childhood influenza disease that helped inform recommendations for expanded childhood influenza vaccination to include children 2-<5 years of age. This innovative research will occur at a unique time of anticipated, widespread childhood nasal influenza vaccine introduction, in a setting that will permit prospective, population-based study of adults and children over multiple consecutive seasons to answer fundamental questions about influenza disease epidemiology and its control.